Detailed Description
The present invention provides a system for stimulating a target tissue with an electrical signal. In one embodiment, the system includes a) a wireless power transfer module operating at a particular resonant frequency, including one or more wearable transmit coils and a portable control circuit, and b) a wireless deformable electrical stimulator for implantation in a subject and operating at the resonant frequency, including at least one receive coil, a power management module, and a stimulation module, the wireless power transfer module generating an alternating magnetic field across the at least one receive coil to induce an alternating voltage, the alternating voltage converted to a steady voltage via the power management module to power the stimulation module to generate the electrical signal.
In one embodiment, the portable control circuit includes a) a rechargeable battery, a power management circuit providing constant current and different voltages, a pulse width modulated signal generator, a full bridge inverter, a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) driver, and one or more matching capacitors, or b) a rechargeable battery, a power management circuit, a signal generator, a power amplifier, and an antenna auto-tuner configured with the one or more wearable transmit coils operating at the resonant frequency.
In one embodiment, the resonant frequency ranges from 100kHz to 1GHz.
In one embodiment, the electrical signal comprises a) monophasic or biphasic voltage pulses or pulse trains, or b) monophasic or biphasic current pulses or pulse trains, or c) charge-balanced current pulses or pulse trains.
In one embodiment, the electrical signal includes one or more of a) a current magnitude of 3mA to 15mA, b) a frequency of 1Hz to 1000Hz, or c) a pulse width of 100 microseconds to 200 milliseconds.
In one embodiment, the stimulation module includes one or more electrodes for delivering the electrical signal to the target tissue.
In one embodiment, the one or more electrodes have one or more of the following features:
a) the one or more electrodes are in a needle-like structure, b) the pitch of each of the one or more electrodes is 0.1mm to 30mm, or c) the one or more electrodes have a length of 50 μm to 300 μm.
In one embodiment, the power management module includes a rectifying circuit for converting the alternating voltage to the regulated voltage, the rectifying circuit being selected from a) a plurality of diodes and capacitors, b) a full bridge rectifier, c) a linear low dropout regulator, d) a boost converter for boosting the regulated voltage, or e) a buck converter for reducing the regulated voltage.
In one embodiment, the wirelessly-deformable electrostimulator is adapted for implantation into the subject through a natural lumen selected from the gastrointestinal tract, the trachea, the urinary tract, or the vagina.
In one embodiment, the wirelessly deformable electrostimulator further comprises a microcontroller for performing one or more of a) setting parameters of the electrical signal, b) controlling the stimulation module, or c) processing wireless communication data via a radio frequency protocol.
In one embodiment, the wirelessly-deformable electrostimulator further comprises a sensing module for monitoring movement or pressure within the subject.
In one embodiment, the wirelessly-deformable electrostimulator further comprises one or more sensing electrodes for measuring electrophysiological signals of the target tissue.
In one embodiment, the one or more wearable transmit coils are selected from a single solenoid, a planar coil, a pair of Helmholtz coils, a pair of solenoid coils braided with a single wire, or a planar coil with an additional resonant coil operating at the same resonant frequency as the planar coil.
In one embodiment, the wirelessly-deformable electrostimulator further comprises a mechanical skeleton;
the at least one receiving coil is an elastic coil woven along the mechanical skeleton.
In one embodiment, the wirelessly deformable electrostimulator is made of a material that allows the electrostimulator to stretch up to 50%.
In one embodiment, the material comprises a dielectric material used as a substrate and encapsulation, and an intrinsic conductive material for circuit traces and contact pads, a) the dielectric material is selected from Polydimethylsiloxane (PDMS), polyurethane (PU), styrene-ethylene-butylene-styrene (SEBS), polyimide (PI), polyethylene terephthalate (PET), or hydrogel, b) the intrinsic conductive material is selected from silver nanowires, carbon nanotubes, gold nanowires, poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), printed copper wire, or gallium-based liquid metal.
The invention also provides a method for delivering the system of the invention to the target tissue. In one embodiment, the method includes the steps of a) inserting a delivery tool through an opening to a desired location, the delivery tool including a balloon and a stent compressed within the delivery tool, the stent being integrated with the wireless deformable electrostimulator, b) releasing the stent integrated with the radiostimulator, and c) inflating the balloon to contact the stimulation module with the target tissue.
In one embodiment, the opening is a natural lumen selected from the group consisting of gastrointestinal tract, trachea, urinary tract, and vagina.
In one embodiment, the delivery tool further comprises a flexible housing, a flexible tip, a blocking ring, and a balloon with a flexible catheter.
In one embodiment, the method includes the steps of a) creating a submucosal tunnel between a mucosal layer and a muscular layer through a standard endoscope, b) assembling the wirelessly deformable electrostimulator with a delivery tool connected to the standard endoscope, c) inserting the wirelessly deformable electrostimulator into the submucosal tunnel, d) configuring the wirelessly deformable electrostimulator to deliver an electrical signal to the target tissue, and e) closing the submucosal tunnel.
In one embodiment, the delivery tool includes a flexible tip and a transparent support for connecting the radio stimulator to the standard endoscope.
In one embodiment, the target tissue is a muscle layer in the gastrointestinal tract, urinary tract, or reproductive system.
The invention provides a wireless power supply electric stimulation system. In one embodiment, the system includes a) a wearable transmitter including a transmitter coil and a control board for wireless power transfer, and b) a radio stimulator including a power management module and a pulse stimulation module. The system may further comprise a sensing module for implementing closed loop electrical stimulation.
In one embodiment, the control board includes a) a rechargeable battery, b) a power management circuit that provides constant current and different voltages, c) a control circuit that includes a pulse width modulated signal generator, d) a full bridge inverter, e) a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) driver, and f) one or more matching capacitors.
In one embodiment, another design of the control board includes a) a rechargeable battery, b) a power management module, c) a signal generator for generating an alternating signal, d) a power amplifier, and e) an antenna auto-tuner that matches the transmit coil to a resonant frequency.
In one embodiment, the geometry of the transmit coil may be a planar structure, a helmholtz coil pair, a single solenoid coil, or a solenoid coil pair, the transmit coil diameter being from 5cm to 80cm. In some embodiments, the transmit coil comprises one planar transmit coil and another independent planar resonant coil. The planar transmit coils and the planar resonant coils all operate at the same resonant frequency. The resonance coil increases the transmission power by increasing the strength of the generated magnetic field.
In one embodiment, the wearable transmitter generates a magnetic field having a frequency of 100kHz to 100 MHz.
In one embodiment, the radio stimulator further includes a receiving coil, one or more pairs of electrodes, or a microcontroller for setting parameters and wireless communication.
In one embodiment, the power management module includes a rectifier circuit that converts alternating current to direct current, and a voltage regulator for providing a regulated voltage.
In one embodiment, the pulse generator module includes a pulse generator for generating a current or voltage pulse signal having a programmable amplitude, frequency and pulse width.
In one embodiment, the pulse generator generates a current or voltage pulse signal having a frequency of 1Hz to 1 kHz.
In one embodiment, the pulse generator generates a current having a magnitude of 3mA to 15 mA.
In one embodiment, the pulse generator generates a current or voltage pulse signal having a pulse width of 100 microseconds to 200 milliseconds.
In one embodiment, the pulse generator generates a charge balanced current pulse signal to avoid tissue damage and electrode erosion.
In one embodiment, the receiving coil includes a ferrite core to improve the efficiency of wireless power transfer.
In one embodiment, each of the one or more pairs of electrodes is a needle electrode for applying electrical stimulation to penetrate tissue.
In one embodiment, the spacing between the one or more pairs of electrodes is 0.1mm to 30mm.
In one embodiment, the one or more pairs of electrodes have a length of 50 μm to 300 μm.
In one embodiment, the shape of the one or more pairs of electrodes is selected from cone, prism or needle.
In one embodiment, the radio stimulator includes a substrate or package made of one or more dielectric materials selected from Polydimethylsiloxane (PDMS), styrene-ethylene-butylene-styrene (SEBS), polyurethane (PU), polyimide (PI), or hydrogel.
In one embodiment, the radio stimulator includes circuit traces and contact pads made of one or more intrinsically conductive materials selected from silver nanowires, carbon nanotubes, gold nanowires, poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), or liquid metal.
The invention provides a method for delivering the wireless power supply electric stimulation system into a natural cavity channel through an endoscope for carrying out minimally invasive electric stimulation treatment, and the wireless power supply electric stimulation system further comprises one or more pairs of electrodes. In one embodiment, the method comprises the steps of a) inserting a delivery tool through a natural orifice, the delivery tool comprising a balloon and a stent compressed within the delivery tool, the stent being integrated with the radio stimulator, b) releasing the stent integrated with the radio stimulator, c) inserting one or more pairs of electrodes into muscle tissue by inflating the balloon.
In one embodiment, the natural lumen comprises the gastrointestinal tract, trachea, urinary tract, or vagina.
In one embodiment, the delivery tool includes a flexible housing, a soft tip for safe contact with tissue, a stop ring, a balloon catheter for inserting the electrode into the tissue, and a handle.
In one embodiment, the present invention provides another endoscopic delivery method, the delivery procedure comprising the steps of i) endoscopically dissecting a mucosal layer of the gastrointestinal tract, creating a submucosal space between the mucosal layer of the gastrointestinal tract and a muscle layer of the gastrointestinal tract, and ii) implanting the radio stimulator into the space, iii) closing the space with a plurality of endoscopic clips.
The invention will be better understood by reference to the following experimental details, but it will be understood by those skilled in the art that the specific experiments are for illustrative purposes only and are not intended to limit the scope of the invention, which should be governed by the following claims.
The present invention provides a radio stimulation system for long-term in vivo electrical stimulation therapy. Referring to fig. 1A, the present invention includes two parts, a wearable transmitter 110 for wireless power transmission with a portable control board 120, and a radio stimulator 100 for applying a pulse signal. An alternating current flows through the transmitting coil 110, thereby generating an alternating magnetic field. However, as distance increases, the magnetic field strength decays rapidly. In addition, biological tissue attenuates electromagnetic energy. Therefore, to achieve wireless power transfer in deep tissues, it is important to properly design the transmit coil 110.
The geometry of the transmit coil 110 has a significant impact on the efficiency of wireless power transfer.
Example 1
In some embodiments, the transmit coil 110 is a single solenoid that can generate a relatively strong magnetic field inside the coil near the central region. The movement or change of direction of the receiver may accidentally induce a higher voltage, causing safety problems. In some embodiments, the transmitting coil 110 is a pair of helmholtz coils, which may generate a uniform magnetic field within their coil areas. However, its magnetic field strength is weaker than that of a single solenoid coil.
In some embodiments, transmit coil 110 is a pair of solenoid coils braided with a single wire. The solenoid coil can generate a uniform and relatively strong magnetic field in its coil region. In some embodiments, the transmit coil 110 has a diameter of 30cm to 80cm to accommodate the body shape of different individuals. In some embodiments, wearable transmit coil 110 is made in the form of a one-piece garment. Referring to fig. 1B, a photograph shows a typical design of a transmit coil 110 on a phantom. Referring to fig. 2A and 2B, the wearable transmit coil 110 may generate a uniform magnetic field within the transmit coil 110 region to power an implanted device in deep tissue.
The implantable medical device 100 is placed within the region of the transmit coil 110. The receiving coil 102 in the electrostimulator 100 induces an alternating voltage at the same frequency as the magnetic field, according to faraday's law.
In addition, the magnitude of the induced voltage is related to the magnetic field strength and the area of the loop enclosed by the receiving coil 102.
In some embodiments, the receiving coil 102 includes a ferrite core to increase the magnetic permeability and thereby increase the induced voltage. In some embodiments, the receive coils 102 are configured in three orthogonal directions and connected in parallel to compensate for efficiency losses due to angle mismatch.
Example 2
The transmit coil 110 is driven by an alternating current having a typical frequency, which is primarily dependent on the transmit coil geometry. Referring to fig. 3, the portable control board 120 includes a rechargeable battery, a power management module 121, a control circuit 122, and an adjustable matching capacitor 123. The control circuit 122 includes a Pulse Width Modulation (PWM) signal generator for providing a square wave signal having an adjustable frequency of 100kHz to 1MHz, a full bridge inverter for converting dc power to ac power to drive the transmit coil, and a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) driver for powering the full bridge inverter.
In some embodiments, the transmitting coil 110 is a planar structure with a resonant frequency of 1MHz to 1GHz. Referring to fig. 4, the signal generator may directly generate an alternating voltage having the resonant frequency of the transmitting coil. Subsequently, the control signal is amplified by a power amplifier and then applied to the transmitting coil. In some embodiments, an antenna auto-tuner is used to connect the output of the power amplifier with the transmit coil 110.
The antenna auto-tuner may automatically adjust the on-board capacitor and inductor to match the transmit coil 110 to the resonant frequency.
In some embodiments, the present invention also provides another independent planar resonator coil. The planar resonant coil is configured in parallel with the transmitting coil 110 to enhance the magnetic field strength. The resonant coil also operates at the same resonant frequency as the transmit coil 110.
Example 3
Referring to fig. 5, the radio stimulator 100 includes a receiving coil 102, a power management module 103-1, a pulse stimulation module 103-2, and one or more pairs of electrodes. As previously mentioned, the receiving coil induces an alternating voltage in the time-varying magnetic field that is unsuitable for powering subsequent circuitry. The alternating voltage is thus converted into a direct voltage by the rectifier circuit. In some embodiments, the rectifying circuit includes a diode that blocks half of the alternating wave, resulting in reduced power conversion efficiency. In some embodiments, the rectifying circuit is a full-bridge rectifier, and the conversion efficiency is better than that of a single diode structure. The converted voltage is smoothed by a capacitor. In addition, the converted voltage is regulated to a stable voltage by a linear low dropout regulator (LDO). In some embodiments, a boost converter boosts the voltage to a higher level to drive the constant current source. In some embodiments, the pulse stimulation module includes a Micro Control Unit (MCU) for wireless communication and pulse parameter setting. And a constant current module converting the voltage pulse into a constant current pulse under different loads.
According to the prior researches, the amplitude, frequency and pulse width of the pulse signals can influence the effect of the electric stimulation treatment. Generally, a pulse train consists of a series of pulse signals with constant intervals and pulse widths. In some embodiments, the pulse is a monophasic signal. However, the accumulated charge may cause muscle fatigue. In some embodiments, the stimulation signal is a biphasic pulse, as shown in fig. 6A, capable of achieving charge balance in the tissue. In some embodiments, the stimulation signal is a voltage pulse. The stimulation signal applies pulses of constant voltage amplitude to the tissue. The charging current may change during stimulation due to parasitic capacitance between the tissue and the electrode. Overcharge presents an associated safety risk. In some embodiments, the stimulation signal is a current pulse, typically having a current amplitude of 3mA to 8mA, as shown in fig. 6B. Current studies indicate that low frequency electrical stimulation is capable of inducing effective muscle movement. Specifically, the frequency is 1Hz to 1000Hz. In some embodiments, both the frequency and pulse width may be adjusted by a Micro Control Unit (MCU), as shown in FIGS. 7A, 7B, 7C, and 7D.
In some embodiments, the radio stimulator includes a rechargeable battery that is rechargeable by wireless means. The battery has a capacity of 1mAh to 2000mAh and can power the entire circuit for a typical period of 5 minutes to 60 minutes.
Example 4
Referring to fig. 8A, in some embodiments, a typical radio stimulator 100 includes a support as a mechanical backbone 101, an elastic coil as a receiving coil 102, and a stretchable pulse generator 103 having one or more pairs of electrodes. Referring to fig. 8B, the elastic coil is made by injecting liquid metal into a single silicone tube. Elastic loops are then woven along the scaffold of the stent. The stretchable pulse generator is made of a soft and flexible material.
In some embodiments, dielectric materials such as Polydimethylsiloxane (PDMS), polyurethane (PU), styrene-ethylene-butylene-styrene (SEBS), and hydrogels are used as substrates and encapsulation. The intrinsic conductive material is used to make circuit traces and contact pads. In some embodiments, the intrinsically conductive material includes, but is not limited to, silver nanowires, carbon nanotubes, gold nanowires, poly (3, 4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS), or liquid metal. In some embodiments, the surface of the electrostimulator is coated with a layer of parylene or a layer of an antimicrobial hydrogel. Referring to fig. 8C, a typical prototype of a stretchable circuit may undergo various deformations including torsion, bending, and stretching. Referring to fig. 8D, the combination of the intrinsically conductive material with the deformable structure enables the integrated radio stimulator to achieve 50% stretching.
Example 5
Referring to fig. 9, the present invention provides a non-invasive endoscopic delivery method via a natural lumen. In some embodiments, the radio stimulator 100 is integrated on one stand. First, the stent with the electrostimulator is compressed within the delivery catheter 130. The delivery catheter is then delivered into the body through the natural orifice. After releasing the stent, its self-expanding stent structure helps retain the device in the narrow channel. Finally, balloon catheter 132 is inflated, releasing the radio stimulator completely and bringing the electrodes into intimate contact with the tissue. In some embodiments, the electrode is made in the form of a microneedle, which is then penetrated through the mucosal layer until the tip of the needle contacts the muscular layer. In some embodiments, the electrode is mounted to an outer layer of the stent. The electrodes may be in direct contact with the tissue when the scaffold applies a normal force to the tissue.
In some embodiments, the electrode may be in direct contact with the target muscle group. In some embodiments, the electrodes are formed as microneedles that enable efficient electrical stimulation through tissue. The length of the microneedles is 300 μm to 800 μm. The microneedles have diameters of 100 μm to 600 μm.
Referring to fig. 10A, the present invention provides a delivery catheter 130 for non-invasive endoscopic delivery. Typically, the delivery catheter 130 includes a balloon 132, a flexible catheter 133, a flexible tip 131, a blocking ring 134, a flexible housing 135, and a handle 136.
Referring to fig. 10B, the stent is compressed and loaded between the flexible catheter 133 and the outer sleeve 135.
During operation, the surgeon holds the handle 136 and pulls the outer sleeve to release the stent.
The stop ring 134 prevents retraction of the stent due to friction during release. In some embodiments, the above procedure is performed under X-rays. The radiolabel may show the position of the stent in an X-ray image. In some embodiments, the delivery catheter includes a small camera disposed on the head of the soft tip. By utilizing the illumination of the LED array around the camera, an endoscopic image is provided for an operation procedure, so that the exposure of ionizing radiation is avoided, and the success rate of carrying out a conveying procedure in a dark environment in vivo is improved.
Example 6
Referring to fig. 11, the present invention provides another design of the radio stimulator 200. Fig. 11A shows a top view of the radio stimulator. The radio stimulator includes a flexible substrate 201, printed receiving coil 202, electronics 203, and a printed antenna 204 for wireless communication. In some embodiments, the radio stimulator may further include a pressure sensing module 205 and/or a rechargeable battery 206. Fig. 11B shows a bottom view of the radio stimulator. The radio stimulator further includes another portion of the printed receive coil 202, one or more electrical stimulation electrodes 207-1, and a reference electrode 207-2. In some embodiments, the radio stimulator may further include one or more electrical sensing electrodes 208.
In some embodiments, the electronic component 203 includes a microcontroller for processing data from the sensor, controlling the stimulation module, and communicating wirelessly via a radio frequency protocol.
Referring to fig. 12A and 12B, the present invention provides a related conveying tool 160. The delivery means comprises a soft tip 162 and a transparent holder 161. As shown in fig. 12C, the delivery tool may be assembled with a standard endoscope 150 to achieve minimally invasive transoral delivery.
Example 7
Referring to fig. 13, the present invention also discloses an endoscopic surgical procedure for minimally invasive implantation. In some embodiments, the radiostimulator 200 is implanted in the esophagus for the treatment of gastroesophageal reflux disease (GERD). As shown in fig. 13A, a submucosal space is first created. An endoscope 150 is inserted through the esophagus 140. An initial incision 141 is made in the mucosal layer of the esophagus. This allows the endoscope to access the wall of the food tube, thereby exposing the muscles. As shown in fig. 13B, the electric stimulator
200 Are carried by the delivery tool 160 and are implanted in the space between the muscular layer and the mucosal layer
141. The exposed electrodes are in direct contact with the esophageal muscles to achieve effective electrical stimulation. At the end of the surgical procedure, the esophageal incision will be closed by the endoscopic clip 170, as shown in fig. 13C.
Example 8
The invention also provides a related application of the radio stimulation system and the endoscope delivery program. The natural lumen includes, but is not limited to, the gastrointestinal tract, urinary tract, trachea, vagina, etc. In some embodiments, the electrostimulator is implanted in the esophagus for treating GERD. In some embodiments, the electrostimulator is implanted in the stomach for treating obesity or gastroparesis. In some embodiments, the electrostimulator is implanted in the small intestine for treating irritable bowel syndrome. In some embodiments, the electrostimulator is implanted near the anal sphincter for treating fecal incontinence. In some embodiments, the electrostimulator is delivered through the urinary tract and implanted into the bladder for treating urinary incontinence. In some embodiments, the electrostimulator is delivered transvaginally for restoring normal function to the pelvic floor muscles.